In general, this invention relates to nucleic acid and amino acid sequences involved in fat metabolism regulation and the use of these sequences as targets for the diagnosis, treatment, and prevention of obesity and obesity-related diseases. In addition, the invention relates to screening methods for identifying modulators of body fat metabolism and the development of treatments for obesity and obesity-related diseases.
Fat metabolism is controlled by a regulatory loop that exists between the central nervous system (CNS) and adipocytes. Adipocytes are specialized cells that store energy in the form of fat droplets, composed primarily of triglycerides. These fat droplets are thought to form by pinching off from membranes of the endoplasmic reticulum. Access to these fat stores is regulated by a protective protein coat, which limits their exposure to cellular lipases, enzymes that breakdown fat. Adipocytes communicate with the CNS via peptide and hormonal signals that carry information regarding the peripheral energy state. In response to these signals, the CNS controls food seeking or satiety behaviors in order to maintain energy homeostasis.
Large gaps remain in our understanding of the cell biology of fat storage, fat droplet biogenesis, and fat droplet size regulation. Moreover, the global regulators of fat metabolism, the interplay of food signals and hormones, and the genetic and environmental factors that influence body weight are still poorly understood. Addressing these deficits is crucial given the devastating impact of obesity on human health throughout the developed world. The dysregulation of body weight is associated with obesity, atherosclerosis, type II diabetes mellitus, and osteoarthritis of body joints. Conservative estimates of economic costs associated with the adverse health effects of obesity range between 2% to 7% of total health costs in the developed world. In the United States, for example, diabetes, one of the diseases associated and exacerbated by obesity, is thought to affect over 16 million individuals at an annual cost of over 92 billion dollars.
As current therapies offer limited effectiveness in treating obesity and obesity-related disease, a need exists for new therapeutic targets.